Polymorphism in intron 4 of HFE does not compromise haemochromatosis mutation results. The European Haemochromatosis Consortium.
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Alleles↗
Biomedical subjects
E Ryan
Publications and source records attributed to E Ryan.
Effect of tamoxifen on sexual functioning in patients with breast cancer.
PURPOSE: To define the incidence of sexual dysfunction in a population of women with breast cancer treated with tamoxifen. PATIENTS AND METHODS: Breast cancer patients with a performance status of 0 to 2 who had been treated with tamoxifen for 2 to 24 months completed the following measures: the Center for Epidemiologic Studies-Depression Scale, the Sexual History Form, and the Breast Cancer Prevention Trial Symptom Checklist. Forty-nine of the participants underwent gynecologic examinations with vaginal smears for determination of estrogen effect. RESULTS: Fifty-seven women were entered onto the trial. Sexual desire, arousal, and ability to achieve orgasm were comparable to norms established in participants in the Tamoxifen Prevention Trial (National Surgical Adjuvant Breast and Bowel Project P-01). Pain, burning, or discomfort with intercourse was reported in 54% of patients and did not correlate with age, surgical treatment of the primary cancer, or chemotherapy. Estrogen effect was seen on the vaginal smears of 34 of 49 participants and was more common in older patients (P = .054). The presence of estrogen effect correlated with negative reactions during sex (P = .02) and vaginal dryness or tightness (P = .046). CONCLUSION: Women treated with tamoxifen in the adjuvant setting experienced symptoms of sexual dysfunction. The individual contributions of chemotherapy and tamoxifen to sexual dysfunction warrant prospective study.
Adult↗
Depressive symptomatology and specificity of social support.
Psychosocial interventions should be based on research which reflects the multidimensionality of psychosocial constructs. This study investigated six categories of social support which were associated with depressive symptomatology in a sample of 531 college students. The Social Provisions Scale was used to measure social support while the Center for Epidemiological Studies-Depression Scale was used to measure depressive symptomatology. Standard multiple regression analysis was used to analyze the variance contributed by each of the six categories of social support found on the Social Provisions Scale to depressive symptomatology. Specifically, the following categories of social support were significantly associated with depressive symptomatology: Reassurance of Worth (for male and female respondents) and Attachment (for females only). Implications for practice and research are discussed.
Adolescent↗
Immunohistochemical detection of mutant p53 protein in regional lymph nodes is associated with adverse outcome in stage II colorectal cancer.
Epidemiologic data identifies a cohort of Duke's B (CRC) patients whose survival more closely matches that of Duke's C. Lymph node micrometastases may account for this discrepancy. Lymph node expression of mutant p53 protein (Mp53P) has been linked to a reduction in survival in Japanese Duke's B patients. We aimed to determine the significance of nodal p53 expression in European Duke's B patients using immunohistochemistry. The study comprised 134 consecutive patients who had resections for CRC between 1984 and 1991. End points were 5 year disease free survival or CRC related death. Thirty-four subjects did not achieve end points and were excluded. We examined tumour and nodal sections for Mp53P by immunohistochemistry and correlated this with survival using a Kaplan-Meier (KM) and a Cox Proportional hazards model (CPHT). Five year survival was 73%. Fifty-eight percent of primary tumours expressed Mp53P. Tumour p53 expression did modulate survival behavior. Twenty-six percent of subjects' lymph nodes expressed Mp53P. Fifty-three per cent of those with positive and 17% of those with negative lymph nodes died of recurrence. The relative risk for nodal Mp53P expression was 3.1. There was a significant univariate relationship between lymph node p53 expression and mortality. (Log Rank p = 0.028). Multivariate analysis also showed a significant relationship with mortality. (CPHT p = .03). We conclude that lymph node expression of Mp53P is associated with increased mortality in Duke's B CRC.
Adult↗
Hemochromatosis in Ireland and HFE.
Sixty patients diagnosed with hereditary hemochromatosis with grade 3 or 4 hepatic iron overload and 18 patients diagnosed with hereditary hemochromatosis who had less than grade 3 hepatic iron overload were examined for the HFE gene mutations, 845A (C282Y) and 187G (H63D). Control samples were obtained from 109 randomly selected individuals. Fifty-six of 60 unrelated hereditary hemochromatosis patients (93%) with grade 3 or 4 hepatic iron deposition were homozygous for the C282Y mutation. Fourteen of the 18 hereditary hemochromatosis patients with <3+ iron deposition (76%) were homozygous for the C282Y mutation. Three of 8 patients who were heterozygous for the C282Y mutation were also heterozygous for the H63D mutation. Thirty-one of 109 control individuals were heterozygous for the C282Y mutation and 27 were heterozygous for the H63D mutation. Our finding that 93% of hereditary hemochromatosis patients who fulfil standard diagnostic criteria are homozygous for the C282Y mutation provides clear evidence that this mutation is strongly associated with hereditary hemochromatosis. The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.
Adolescent↗
Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children.
Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.
Antigens, Bacterial↗
A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis.
The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough. However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis. Classical approaches based on measurement of antibody responses to individual antigens failed to define an immunological correlate of protection. A reliable animal model, predictive of acellular and whole-cell pertussis vaccine potency in children, would facilitate an elucidation of the mechanism of immune protection against B. pertussis and would assist in the regulatory control and future development of pertussis vaccines. In this study, we have shown that the rate of B. pertussis clearance following respiratory challenge of immunized mice correlated with vaccine efficacy in children. Using this model together with mice with targeted disruptions of the gamma interferon (IFN-gamma) receptor, interleukin-4 or immunoglobulin heavy-chain genes, we have demonstrated an absolute requirement for B cells or their products in bacterial clearance and a role for IFN-gamma in immunity generated by previous infection or immunization with the whole-cell pertussis vaccine. The results of passive immunization experiments suggested that protection early after immunization with acellular pertussis vaccines is mediated by antibody against multiple protective antigens. In contrast, more complete protection conferred by previous infection or immunization with whole-cell pertussis vaccines reflected the induction of Th1 cells. Our findings suggest that the mechanism of immunity against B. pertussis involves humoral and cellular immune responses which are not directed against a single protective antigen and thus provide an explanation for previous failures to define an immunological correlate of protection.
Animals↗
SDM95: increase nursing ratios without adding cost through economic sizing and staffing to the 95th percentile.
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Hospital Bed Capacity↗
A respiratory challenge model for infection with Bordetella pertussis: application in the assessment of pertussis vaccine potency and in defining the mechanism of protective immunity.
The evaluation of vaccines for human use usually requires the development of appropriate animal models and the definition of laboratory correlates of immunity. Traditionally whole cell pertussis vaccines have been controlled by using an active mouse protection test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency of the new generation acellular pertussis vaccines. In the present study we demonstrate that a murine respiratory challenge model for infection with B. pertussis is suitable for assessing the potency of acellular and whole cell pertussis vaccines. To allow standardization of different vaccines we have expressed the area under the clearance curve for immunized mice as a ratio of that for non-immunized controls to obtain a potency index. A comparison of estimated vaccine efficacy in children with potency in the murine model results in a highly significant correlation (r = 0.976, p < 0.001). Furthermore, we have used this model to define the protective mechanism of immunity against respiratory infection with B. pertussis and demonstrate a requirement for both specific T and B cells. In accordance with studies in humans, no clear relationship was observed between monotypic serum antibody responses against the putative protective antigens of B. pertussis and protection. In contrast, the most potent protection was observed when the T cell response is polarized to the Th1 subtype.
Animals↗
Melatonin modulates vascular smooth muscle tone.
The molecular cloning of a family of melatonin receptors has created a renewed interest in the diverse actions of the hormone melatonin. The radioligand 2-[125I]iodomelatonin has identified potential sites of action for melatonin throughout the central nervous system and periphery of numerous species. Interestingly, in addition to the suprachiasmatic nucleus (the "biological clock"), 2-[125I]iodomelatonin binding sites have been localized to the rat caudal and cerebral arteries. Furthermore, in vitro, melatonin has been shown to induce a concentration-dependent vasoconstriction of rat caudal and cerebral arteries, and pig and human coronary arteries. The lack of melatonin receptor subtype-selective agonists and antagonists prevents the full pharmacological characterization of these responses. The physiological significance of the in vitro vasoconstrictive properties is far from clear, however; in rats, melatonin has been shown to reduce cerebral blood flow. The widespread use of melatonin warrants appropriately designed studies to probe the role of melatonin and its receptors in the modulation of in vitro vascular tone.
Animals↗
Building an effective corporate compliance plan.
Corporate compliance plans are essential for healthcare organizations to cope with, and perhaps even stave off, investigations arising from allegations of illegal business practices. Initial development and implementation of a corporate compliance plan can be facilitated through four steps: determining the content of the code of conduct, determining how the code will be distributed, assigning responsibility for implementing the plan, and appointing a compliance task force to guide the implementation process. Special attention should be paid to education requirements of the United States Sentencing Guidelines to see that all employees understand and can apply provisions of the plan.
Employee Discipline↗
Professional needs of palliative care nurses in New South Wales.
A survey of 108 palliative care nurses practising in New South Wales, Australia, was undertaken to explore their professional needs and clinical knowledge. Opportunity for improved training was the most frequently nominated professional need. Only 12% of the sample had postgraduate qualifications in palliative care and fewer than 20% were currently undertaking postgraduate training. Sixty-three per cent of nurses indicated that a lack of opportunity for formal study was a problem for them. The results of the knowledge survey revealed a need for additional training. Many nurses did not have the clinical knowledge identified as minimal by an expert committee. Those nurses who had a postgraduate qualification in oncology scored more highly on the knowledge questionnaire than did those whose general nursing training was undertaken outside Australia. The implications of these findings for training and other professional support are discussed.
Adult↗
Fructosamine concentrations in hyperglycemic cats.
The aims of this study were 1) to establish a reference range for fructosamine in cats using a commercial fructosamine kit; 2) to demonstrate that the fructosamine concentration is not increased by transient hyperglycemia of 90 min duration, simulating hyperglycemia of acute stress; and 3) to determine what percentage of blood samples submitted to a commercial laboratory from 95 sick cats had evidence of persistent hyperglycemia based on an elevated fructosamine concentration. Reference intervals for the serum fructosamine concentration were established in healthy, normoglycemic cats using a second generation kit designed for the measurement of the fructosamine concentration in humans. Transient hyperglycemia of 90 min duration was induced by IV glucose injection in healthy cats. Multisourced blood samples that were submitted to a commercial veterinary laboratory either as fluoride oxalated plasma or serum were used to determine the percentage of hyperglycemic cats having persistent hyperglycemia. The reference interval for the serum fructosamine concentration was 249 to 406 mumol/L. Transient hyperglycemia of 90 min duration did not increase the fructosamine concentration and there was no correlation between fructosamine and blood glucose. In contrast, the fructosamine concentration was correlated with the glucose concentration in sick hyper- and normoglycemic cats. It is concluded that the fructosamine concentration is a useful marker for the detection of persistent hyperglycemia and its differentiation from transient stress hyperglycemia. Fructosamine determinations should be considered when blood glucose is 12 to 20 mmol/L and only a single blood sample is available for analysis.
Animals↗
Persistent flat-topped papules on the extremities. Acrokeratosis verruciformis (AKV) of Hopf.
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Adult↗
Simultaneous measurement of monoamines, metabolites and amino acids in brain tissue and microdialysis perfusates.
A high-performance liquid chromatographic method with coulometric array electrochemical detection is described for the simultaneous analysis of monoamines, their metabolites and o-phthalaldehyde (OPA)-derivatized amino acids. This method has been used to examine metabolite levels in both striatal tissue homogenates and striatal microdialysis perfusates. An aliquot of sample was initially analyzed for monoamines and metabolites by isocratic elution and electrochemical detection on a serial electrode array of eight coulometric flow-through graphite electrodes (0 to 490 mV; 70-mV increment). The remaining sample was derivatized pre-column with OPA-beta-mercaptoethanol and after column switching was analyzed for amino acids on a second isocratic system with electrochemical detection on four electrodes. Metabolites were then identified based on their retention time as well as electrochemical behavior across the arrays. The analysis, derivatization procedure, column switching, data reduction and peak identification were fully automated. The limit of detection for striatal tissue homogenates was approximately 1.38 ng/g wet weight for the monoamines and 8.25 ng/g wet weight for amino acids. The limit of detection for striatal perfusates was approximately 2.5 pg per 20-microliters sample for the monoamines and 15 pg per 20-microliters sample for the amino acids with analysis completed within 25 min making it ideal for microdialysis samples.
3,4-Dihydroxyphenylacetic Acid↗
Analysis of phenolic and flavonoid compounds in juice beverages using high-performance liquid chromatography with coulometric array detection.
Analysis of phenolics and flavonoids in juice beverages using reversed-phase HPLC with coulometric array detection is described. Sixteen serial coulometric detectors were used for on-line resolution of co-eluting compounds and generation of voltammetric data. Within each class of compounds, oxidation potential corresponded to specific substitution patterns where: catechol < methoxycatechol < monohydroxyl < methoxyl. Twenty-seven standard compounds were resolved in a 45-min run. The limits of detection were in the low ng/ml range with a linear response range of at least three orders of magnitude. Intra-run retention time variation was < 1% (R.S.D.) and adjacent sensor response ratios varied by < 5% (R.S.D.). The utility of this technique in generating multivariate data for differentiation of juices and juice mixtures is shown.
Analysis of Variance↗
Evidence for bimodal distribution of breast carcinoma ER and PgR values quantitated by enzyme immunoassay.
Breast carcinoma oestrogen receptor (ER) and progesterone receptor (PgR) values obtained by radioligand binding assays have commonly been observed to have approximate log-normal distributions. We examined the distribution of log-transformed receptor values obtained by enzyme immunoassay for 5468 primary breast carcinomas in five Ontario laboratories. In each laboratory, it was found that the frequency histograms for the log transformed receptor values were not unimodal, and generally were suggestive of bimodality. This was not affected by stratification by age or inferred menopausal status (< or = 49, > or = 50 years), and could not be explained by kit characteristics. However, the low point in the distribution varied from 5 to 63 fmol/mg cytosol protein, depending on the receptor, patient age and laboratory. The tendency towards biomodality was more distinct for ER than for PgR. It remains to be determined whether the low points on the frequency histograms have clinical relevance for discriminating between hormone-sensitive and hormone-insensitive tumours.
Adult↗
Cutaneous epithelioid hemangioendothelioma without systemic involvement.
Epithelioid hemangioendothelioma (EH) is a unique vascular tumor characterized histologically by epithelioid endothelial cells. A case of EH arising from the dermis and presenting as a nodule of the palm is described. To our knowledge, this is the third report of a cutaneous presentation of EH and the first report of a patient with this rare neoplasm with solitary cutaneous involvement. A review of the literature is also presented.
Adult↗